Symmetrical diarylized guanidine compounds



Patented 1m s, 1928.

l iz lll HERBERT BGHOTTE, F BEBLIN-WILMERSDORF, GERMANY, ASSIGNOR TO THE FIRM CHEHISOHE FABBIK AUF ACTIEN VORMALS E. SGHERING, OF BERLIN, GERMANY.

SYMHETBICAL DIARYLIZED GUANIDINE COIHTPOlINDS.

Bio-Drawing. Application filed November 22, 1926, aerial No. 150,16fi, and in Germany November 30, 1925.

My invention refers to the production of uanidinecompounds.

I have found that if a salt of an isothio carbamide is caused to act on an -aryl amine in the proportion of at least two molecules of the aryl amine to one molecule of the carbamide, asymmetrical diarylized guanidine is formed, the second aryl nucleus not entering into combination with the nitrogen corresponding atom with which the first aryl nucleus is combined, but with the second primary amino group of the guanidine.

The new compounds thus obtained are useful for therapeutical urposes, quite especially in the form 0 salts which are readily soluble in water..

Example 1.-- 80 gra ns aniline are heated in the presence of a small quantity of water to 100-130 C. with 72 grams S-ethylisothiocarbamide hydrobromide (or with uantities of 'S-methyhisothiocarbamide hydroiodide or S -benzyl-isothiocarbamide hydrochloride, and so on) until the separation of merca tan has come to an end. lhe reaction pro not is freed by ex traction with ether from the surplus of aniline and the residue is rendered alkaline with caustic soda solution. Froin this residue the symmetric diphenyl guanidine separates out in the form of prisms which dissolve in water onl with great difficulty, but are readily solub e in alcohol and ether. The melting points is l-l8l49 C.

Ewample 2.10.8 grams S-ethyl-isothiocarbamide hydrobromide are heated with 9 grams 'o-anisidine and a small quantity of water in the manner above described. The mass obtained, which has a red brown color, is freed from the o-anisidine in excess means of ether and benzene, The symmetrical his-(o-methoxy phenyl)-guanidine hydrobromide l! l? yer-fang BB: Nh

con, cine which ultimately solidifies and is soluble in water only with diiiiculty, while being readily soluble in organic solvents. When boiled with an alkali it is converted into the corresponding carbamide.

Various changes may be made in the details disclosed in the foregoing specification without departing from the invention or sacrificing the advantages thereof.

I claim i 1. -The method of making a symmetrical diaryl guanidine' compound, comprising causing a salt of an isothiocarhamide ether. to react With an aryl amine in the propor 'tion or at least two molecules of the aryl amine to one molecule of the ether.

2. The method, of making symmetrical his- (o-methoxyphenyl) guanioline compris in causing a salt of S-ethyl-isothiocarbamlde to act at a temperature at l00-l50 C. in the presence of a small quantity of water on o-anisidine until no more mercaptan is develo ed, and precipitating with an alkali. 

